Bone is the most common site of metastasis, and although low proliferation and immunoediting at the early stage make existing treatment modalities less effective, the microenvironment-inducing behaviour could be a target for early intervention. Here we report on a spatiotemporal coupling interaction between tumour cells and osteoclasts, and named the tumour-associated osteoclast ‘tumasteoclast’—a subtype of osteoclasts in bone metastases induced by tumour-migrasome-mediated cytoplasmic transfer. We subsequently propose an in situ decoupling–killing strategy in which tetracycline-modified nanoliposomes encapsulating sodium bicarbonate and sodium hydrogen phosphate are designed to specifically release high concentrations of hydrogen phosphate ions triggered by tumasteoclasts, which depletes calcium ions and forms calcium-phosphorus crystals. This can inhibit the formation of migrasomes for decoupling and disrupt cell membrane for killing, thereby achieving early prevention of bone metastasis. This study provides a research model for exploring tumour cell behaviour in detail and a proof-of-concept for behaviour-targeting strategy.

骨是最常见的转移部位，尽管早期的低增殖和免疫编辑使现有的治疗方式效果较差，但微环境诱导行为可能成为早期干预的目标。在这里，我们报告了肿瘤细胞和破骨细胞之间的时空耦合相互作用，并将肿瘤相关破骨细胞命名为“tumasteoclast”——肿瘤迁移体介导的细胞质转移诱导的骨转移中破骨细胞的一种亚型。随后，我们提出了一种原位解偶联杀伤策略，其中封装碳酸氢钠和磷酸氢钠的四环素修饰的纳米脂质体被设计为专门释放由破骨细胞触发的高浓度磷酸氢根离子，从而消耗钙离子并形成钙磷晶体。这可以抑制解偶联迁移体的形成并破坏细胞膜进行杀伤，从而达到早期预防骨转移的目的。这项研究为详细探索肿瘤细胞行为提供了一个研究模型，并为行为靶向策略提供了概念验证。